The Landmark Study That Transformed the Global AIDS Strategy

Scientists and Policy Makers Endorse Immediate Start of HIV Therapy for All

AIDS vigil
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There has long been debate among policy makers, researchers, and clinicians alike as to whether starting HIV therapy at the time of diagnosis might have benefits to the patient, both in terms of better long-term health and the avoidance of both HIV- and non-HIV-associated illnesses.

A landmark study released by the New England Journal of Medicine on July 20, 2015 put the debate to rest by concluding that immediate treatment would not only reduce the likelihood of illness and death by 57% but do so irrespective of a person’s age, race, sex, viral load, region of the world, economic status or immune status (as measured by the so-called CD4 count).

Previous to the study, antiretroviral therapy (ART) was recommended when an individual’s CD4 count dropped beneath a certain threshold (generally below 500 cells/mL or, in some countries, below 350 cells/mL).

The new research—called the Strategic Timing of Antiretroviral Therapy (START) trial—was designed determine whether treatment at higher CD4 counts might confer to better health outcomes without increasing a patient’s risk of cardiovascular, kidney or other non-HIV-associated diseases.

START Study Design and Results

The first complete results of the START trial, presented at the 2015 International AIDS Conference in Vancouver by Dr. Jens Lundgren of the Copenhagen HIV Program, were highly anticipated after it is was announced in May that the study would be terminated prematurely due to overwhelming evidence of it positive benefits.

The study, which was initiated in 2009, recruited 4,685 HIV-positive men and women from 215 sites in 35 countries, all of whom had baseline CD4 counts of over 500 cells/mL. The median age was 36 years, while 27% of the participants were women.

Patients were then divided into two groups: one in which ART was started immediately and another in which ART was deferred until either the person’s CD4 count dropped below 350 cells/mL or there was a development of serious AIDS-related illness or death.

By the time of the study’s termination, 50 serious AIDS-related events were noted among the deferred arm of the study, nearly four times more than were noted among the patients given immediate ART (14). Similarly, there were almost twice as many serious non-AIDS related events (29) than were seen in the immediate (ARM).

Tuberculosis, lymphoma and Kaposi sarcoma (KS) were the three most predominant AIDS-related events seen in study participants, with 62% of these occurring in African participants. The serious non-AIDS-related events were primarily cancer, cardiovascular disease (CVD) and death.

By group, the majority of adverse events were seen in older patients, which may seem reasonable given the higher rates of cancer and CVD among an older population in general. Surprisingly, smoking did not appear to alter the results, suggesting that immediate ART was as of much benefit to smokers than to non-smokers.

Perhaps the most unusual finding, however, was that adverse events tended to occur not among patients with lower CD4 count, as would be expected, but among those with higher CD4 counts. While researchers were not able to fully explain the results, the findings echoed earlier studies which had suggested that CD4 counts alone may not provide a full portrait of a person’s immune vulnerabilities.

In his presentation, Dr. Lundgren called for research into novel approaches to immune monitoring to better understand the mechanisms for these otherwise premature AIDS-related and non-AIDS-related events.

START Considered a Defining Moment in AIDS Research

The START trial first gained importance in 2011 when another study, the HPTN 052, demonstrated that taking ART dramatically reduced the risk of transmitting the virus from an HIV-infected person to an uninfected sexual partner—a strategy popularly known as Treatment as Prevention, or TASP.

In light of these two results, leaders at the 2015 IAS Conference issued the so-called Vancouver Consensus statement, declaring that "(all) people living with HIV must have access to antiretroviral treatment upon diagnosis."

While the leaders acknowledged numerous barriers to implementation—not least of which includes an immediate, annual $8-10 billion increase in funding from global partners and donor countries—they insist the strategy can ultimately "end" the epidemic as we know it by as early as 2030. 

In commenting on the START results, Kate Thomson of the Global Fund declared the  trial marked a "defining moment " in the global fight against HIV, one which still sees over two million new infections and 1.2 million deaths each year.

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